1. Field of the Invention
The present invention relates to a method of for the prevention or minimization of wrinkles in facial skin and neck areas of a patient.
2. Reported Developments
Applicant has discovered and filed patent applications on the following methods utilizing safflower seeds or extracts thereof:
Treatment of rheumatoid-based arthritic diseases and menopause, issued as U.S. Pat. No. 5,753,266;
Treatment of inflammaotry diseases, issued as U.S. Pat. No. 5,968,519; and
Prevention or minimization of the effect of catabolic illness by enhancing the immune response of a patient, U.S. application Ser. No. 09/364,413.
In the course of further investigation and experimentation using volunteers, applicant has discovered that safflower seeds or extracts thereof can be used to prevent or minimize wrinkles in the facial skin and neck of a patient.
Rheumatoid arthritis (hereinafter sometimes referred to as RA) is a common type of arthritis that causes inflammation in the lining of the joints and sometimes other internal organs. RA tends to persist for many years, typically affects many different joints throughout the body, and ultimately can cause damage to cartilage, bones, tendons and ligaments. RA is a chronic, inflammatory, connective-tissue disorder affecting more than five million individuals in the U.S., and accounting for considerable disability in terms of missed work, lost wages, and reduced productivity. The disease can occur at any age, but it most commonly begins in the third to fifth decades of life.
The American College of Rheumotology has established criteria of the diagnosis of rheumatoid arthritis which include:
1. Morning stiffness lasting at least one hour;
2. Swelling of three or more joints;
3. Swelling of the wrist, metacarpophalangeal or proximal interphangeal joints;
4. Symmetric joint swelling;
5. Rheumatoid nodules;
6. Positive rheumatoid factor; and
7. Changes on hand radiographs typical of rheumatoid arthritis that must include erosions or unequivocal bony decalcification.
The correct diagnosis of RA is essential for the clinician and involves certain clinical, laboratory and radiological findings. The diagnosis is influenced by the age and sex of the patient, the pattern of joint involvement, the onset and course of the disease and extrarticular manifestations.
In contrast to rheumatoid arthritis, osteoarthritis (hereinafter sometimes referred to as OA), the illness most often contemplated in the differential diagnosis, usually begins after the age of 50 and affects men and women equally. The joints involved in OA are different from those in RA and are not necessarily symmetrically affected. In OA, joint pathology is primarily mechanical, and synovial membrane inflammation is minimal.
As pertaining to the present invention certain other inflammatory arthritis is differentiated from RA as listed in Table I.
With varying clinical significance, RA can at times affect other areas of the body. The most characteristic of these so-called extra-articular manifestations are rheumatoid nodules. They can be found subcutaneously in up to 25% of rheumatoid patients, especially over extensor surfaces and in pressure areas. Common sites include the olecranon regions, fingers, Achilles tendons, the sacrum and the occiput. The presence of subcutaneous nodules is helpful diagnostically, because they are uncommon in the other forms of inflammatory arthritis. Nodules can also occur in visceral organs, including the lungs and the heart.
As discussed above, the primary cause of RA is unknown. It is thought to be triggered by the presence of an as yet unidentified antigen(s) in an immunogenetically susceptible host, and the nature of the antigen responsible for the arthritic reactions in RA has yet to be clearly established.
Heretofore medical management of RA involved three general approaches.
The first is the use of aspirin and other nonsteroidal anti-inflammatory analgesics, and low-dose glucocorticoids to control the symptoms and signs of the local inflammatory process. These agents are rapidly effective at mitigating symptoms and signs, but they appear to exert little effect on the progression of the disease.
A second group of drugs includes a variety of agents that have been classified as the disease-modifying drugs. These agents appear to have the capacity to decrease elevated levels of acute phase reactants in treated patients, and therefore, are thought to modify the destructive capacity of the disease.
The third class of agents includes the immunosuppressive and cytotoxic drugs that have bee shown to ameliorate the disease process in some patients. These last two classes of agents, however, often cause serious side effects including the development of heart and liver diseases, increase in blood pressure, blindness and malignant neoplasms.
The prior art treatment of RA is based on the following two principles: first, RA is a systemic connective-tissue disorder that is not remediable solely through local measures. Second, RA is a progressive disease that can potentially lead to severe cartilage and bone destruction, organ damage, and decreased life expectancy. Current regimens are predicated on controlling the immune system disturbance to reduce joint discomfort and destruction and this to maintain the patient""s activities of daily living.
Available drug preparations for the treatment of RA include the following.
1) NSAIDS: Nonsteroidal Anti-Inflammatory Drugs
Pharmacologic treatment of RA has advanced steadily in the past several decades, but none of the agents used so far can cure RA. Aspirin remains an important part of the treatment program for many people with RA. To be effective, it must be given in doses much higher than commonly used as an over-the-counter remedy for minor aches and pains. Compared to other similar NSAIDS, aspirin is less expensive and its blood level can be precisely measured. However, it can cause stomach problems in many people. Many physicians recommend the use of enteric (coated) forms of aspirin.
NSAIDS are a large group of drugs that have mechanisms of action similar to aspirin. Like aspirin, these medications can relieve some of the pain associated with RA temporarily. The NSAIDS are the most frequently recommended antirheumatic medications, and the first line of therapy in RA. As a result of the capacity of these agents to block the activity of the enzyme cyclooxygenase and therefore the production of prostaglandins, prostacyclin and thromboxames, they have analgesic, anti-inflammatory and antipyretic properties. Table II lists the most commonly prescribed NSAIDS.
Table III lists the commonly prescribed NSAIDs by classification, half-life and dosage range.
These agents are all associated with a wide spectrum of toxic side effects. A common side effect of these drugs is bleeding from the stomach. Overall dose is limited by such gastrointestinal erosions, as well as azotemia, platelet dysfunction, exacerbation of allergic rhinitis and asthma, liver function abnormalities, some renal and cardiovascular irritation, and CNS toxicity like tinnitus, although patients occasionally differ unpredictably in their response to an individual NSAID.
An individual""s response to the various NSAIDS is quite variable. Gastrointestinal ulcerations develop in 0 to 30% of NSAID-treated patients. Duodenal lesions are less common than gastric ulcers. The nephrotoxic effects of NSAIDS are well documented. Several mechanisms leading to renal prostaglandin synthesis may adversely affect renal blood flow and in certain situations, lead to acute insufficiency. At high risk are patients with minor or major pre-existing changes in renal function, such as those with changes related to aging, diabetes mellitus, hypertension, congestive heart failure, use of diuretics or low salt diet, cirrhosis, and chronic renal failure of any other cause.
Once the diagnosis of rheumatoid arthritis has been firmly established as an insufficient response to local measures and NSAIDS determined, the addition of DMARDs (disease modifying antirheumatic drugs) to the regimen is normally considered. These drugs include gold compounds, penicillamine, hydroxychloroquine, methotrexate and azathioprine. Estimated rates of efficacy and toxicity of these remittive agents is shown in Table IV.
The ability of these drugs to really modify the disease process is controversial. Unlike NSAIDS or Corticosteroids, their onset of action is gradual over weeks to months. In addition, well-defined toxicity""s can occur with these drugs, and clinical laboratory monitoring must be judicious. The response rate to the DMARDs is also variable, and patients may gradually lose their positive benefits over time. They exert minimal direct nonspecific anti-inflammatory or analgesic effects, and therefore, NSAIDS must be continued during their administration, except in a few rare cases when true remissions are induced with them. Remittive agents have a wide spectrum of biological effects, but their exact mechanism of action in RA is unknown. Each is associated with considerable toxicity and there is minimal evidence that disease-modifying drugs actually retard the development of bone erosions or facilitate their healing. A brief description of each drug follows.
A. Hydroxychioroquine (Plaquenil)
Hydroxychloroquine is a drug originally developed for the treatment of malaria that has also been used for many years to treat RA and has been somewhat effective among patients with mild to moderate RA. Drug-related adverse effects include gastrointestinal disturbances, skin rash, retinal pigmentary changes and visual impairment, and are more frequently found among older patients. Regular eye examinations once or twice a year because of potential damage to the retina is recommended, and Hydroxychloroquine must be discontinued at the first evidence of visual impairment.
B. Penicillamine (Depen, Cuprimine)
Penicillamine is equally effective in elderly and in younger RA patients. However, its rate of severe toxicity is high, and some adverse effects such as serious skin rashes and taste abnormalities are more common in the older patient. Other adverse effects include nephropathy, bone marrow suppression, gastrointestinal disturbance, autoimmune syndromes, liver toxicity and neuropathy secondary to pyridoxine (vitamin B6) deficiency. Penicillamine is also a slow-acting drug, thus benefit may be achieved only after 3 to 6 months of use. Patients should be monitored with blood counts and urine analyses weekly for the first 4 weeks, then every 4 weeks, with tests of muscle and liver enzymes biannually.
C. Parenteral Gold (Myochrysine, Solganal)
Parenteral gold (intramuscular sodium aurothiomalate or aurothioglucose) has been widely used for 60 years for the treatment of RA. However, gold may lose its effectiveness over time in people who seem to benefit at first. furthermore, it often takes three to six months to determine whether a person is getting benefits from gold salts and the drug is often discontinued for lack of improvement after the 1000 mg dose is reached.
In some people gold treatment may slow down damage to cartilage and bone. This small group of people with RA experience long-lasting improvement on gold injections, which are given weekly or six months or longer, and can later be tapered to once every three weeks. However, the efficacy of parenteral gold is also hampered by its high rate of toxicity, relative to other remittive agents. Adverse reactions most frequently encountered include skin rashes, oral ulcers, nephropathy and bone marrow suppression. Less common reactions are pneumonitis, enterocolitis and hepatitis. Patients should be monitored with blood counts and urine analyses before each injections, as well as physical examination to look for skin rash and oral ulcers.
D. Auranofin (Ridaura)
Auranofin (oral gold) therapy appears to be less toxic but also less effective than parenteral gold. The spectrum of adverse effects is similar to that of parenteral gold. However, the frequency of gastrointestinal disturbances, especially diarrhea, is higher, while frequency of other toxicity""s may be lower. Auranofin""s beneficial effects may be achieved only after 2 to 6 months of use. Patients should be monitored with blood counts and urine analyses biweekly initially, then every month.
E. Sulfasalazine (Azulfadine)
Sulfasalazine has been reintroduced recently as a remittive agent in RA. It also appears to have a high toxicity ratio, with adverse effects including skin rash, gastrointestinal disturbances, bone marrow suppression, haemolysis, headaches, hepatotoxicity and pneumonitis. It is contraindicated in patients with a known hypersensitivity to sulfur drugs. There is a paucity of data regarding efficacy profiles. More elderly patients discontinue treatment mainly because of gastrointestinal adverse effects. Patents should be monitored with blood counts, urine analyses and liver function tests biweekly initially, then every month. Sulfasalazine is not yet approved by the FDA for treatment of RA.
F. Azathioprine (Imuran)
Azathioprine is an immunosuppressive drug that has gained widespread use in RA. Data are insufficient to asses its efficacy or toxicity profiles in the general population. It can help RA by suppressing overactivity of the immune system but also can increase susceptibility to certain infections and lower blood counts. Common adverse effects include the aforementioned and increased risk of infections and the development of malignancies. It is recommended that elderly patients be monitored with blood counts and liver function tests biweekly initially, then every month.
G. Methotrexate (Rheumatrex)
Since the mid-1980""s, methotrexate has become the most prescribed remittive agent for RA in many rheumatology centers. This is due to its higher rate of efficacy and toxicity ratio relative to other remittive agents, its rapid onset of action (mostly within 1 month) and convenient scheduling, with once-weekly dosage of pills or injections. It works more quickly than gold and maintains control of the disease in a larger group population. Unlike gold, methotrexate cannot be taken less frequently after the first 6 to 12 months but instead, must be continued every week.
For the above reasons, methotrexate has proved comparatively effective in controlling joint inflammation in many patients with RA and is often chosen first, especially for individuals with rapidly progressive disease. However, long-term trials have indicated that methotrexate does not induce remission, but rather suppresses symptoms while it is being administered. The other agents are tried when less severe inflammation occurs and if methotrexate has failed or has to be discontinued because of toxicity. However, age is positively related to methotrexate toxicity. Adverse effects include oral ulcers, gastrointestinal symptoms, alopecia, hepatotoxicity, pneumonitis and bone marrow suppression. Transient elevations of liver enzymes occur frequently, but their long term significance is unclear, since they sometimes correlate with histological abnormalities. Fibrosis has been reported in 30 to 52% of patients but there have been fewer reports of cirrhosis. Moreover, sequential liver biopsies in patients continuing methotrexate therapy showed evidence of progression of abnormalities in hepatic architecture. Patients with pretreatment liver abnormalities, alcoholism or lung diseases seem to be at increased risk of developing toxicity in the liver and lung, respectively. Patients should be monitored with blood counts and liver function tests weekly initially, then every month. Kidney functions tests and chest x-ray or pulmonary functions tests should be performed once or twice per year.
H. Alkylating Agents
Alkylating agents cyclophosphamide (Cytoxan) and chlorambucil are very powerful immunosuppressive drugs that are rarely prescribed for the treatment of RA. Despite some proof of efficacy, they can be recommended only for patients with severe, relentless, active RA, not responding to other remittive agents or with serious complications outside the joint such as vasculitis (blood vessel inflammation). This is due to their great risk of frequent and sometimes life-threatening adverse effects, which includes bone marrow suppression, increased susceptibility to infection, and up to a 10-fold increase in the incidence of neoplasia. Other adverse effects are gastrointestinal intolerance, alopecia, pneumonitis and haemorrhagic cystitis. Patients should be monitored with weekly blood counts.
I. Corticosteroids
The role of Corticosteroids (cortisone, prednisone, and other similar medications) in RA is still debated by physicians. In the short run, low dose corticosteroids such as prednisone 5 to 10 mg or cortisone are somewhat effective in some RA patients. However, prolonged administration should be avoided because of long term adverse effects, even with low dosage regimens. These side effects are serious and with respect to cortisone, can include easy bruising, osteoporosis (thinning of the bones), cataracts, weight gain, increased susceptibility to infections, diabetes and high blood pressure. Dosage as low as 5 mg/day of prednisone may suppress the hypothalamic-pituitary-adrenal axis. Other problems include sodium and fluid retention, hypertension, hyperglycaemis, osteoporosis, infections and skin changes.
For any patient taking a corticosteroid on a regular basis, careful attention must be directed to proper calcium, vitamin and hormone regulation. Corticosteroids sometimes are given an injection into one or more joints or other areas of inflammation. Such injections may have harmful side effects on the joints if given more than a few times a year as shown in Table V.
To date, long term management of RA has required a careful balance of benefit and risk; the estimated relative efficacy and toxicity of remittive agents in patients. Usually therapy begins with the least toxic medications and NSAIDS are prescribed first. If further therapy is needed, hydroxychloroquine, auranofin, or sulfasalazine is added in patients with mild to moderate RA. Methotrexate or parenteral gold may be given in patients with moderately severe disease, or with disease unresponsive to the former remittive agents. Penicillamine, azathioprine and particularly the alkylating agents are reserved for patients with refractory disease. Low dosage prednisone is added for limited periods of time as indicated above, while pulse-therapy with parenteral Corticosteroids can help in the induction of remission of RA. These can be supplemented with intra-articular corticosteroid treatment.
We have now discovered compositions and methods for the treatment of patients suffering from minor to advanced arthritic conditions. The compositions of the present invention effectively replace alternative, state-of-the-art pharmaceutical remedies for persons suffering from rheumatoid arthritis and rheumatoid-related inflammatory diseases.
We have also discovered that the compositions of the present invention can be effectively used in a regimen for delaying of menopause.
Menopause is defined in medial dictionaries as the cessation of menstruation in the human female. Menopause is better described as a transition period marking the closure of reproductive life, usually occurring during mid-life. The average age at last menstrual period in the U.S.A. is 51, though any time between age 40 and 59 falls within the realm of normal. As menopause approaches, the ovaries begin to fail and there is a sudden dip in the female sex hormones, estrogen and progesterone, which causes the cessation of menstruation. About 75 to 80% of women have some symptoms related to the suddenness of estrogen withdrawal.
Throughout most adult lives, the menstrual cycle operates in an expected way, with hormones ebbing and flowing at levels just high enough to keep the system in a comfortable balance. In early puberty, anovulatory cycles (months in which no egg has been produced by the ovary) are signaled by heavier and longer bleeding than normal. The same happens in reverse as menopause approaches. In the months in which ovulation does not take place, periods tend to be heavier and longer. As premenopause (the time when periods are still regular) moves towards the perimenopause (the transition phase between regular periods and no periods at all), monthly events become more unpredictable.
As used herein the definitions of certain terms are as follows.
The word xe2x80x9cclimactericxe2x80x9d describes the ongoing changes and symptoms of menopause, as it refers to a phase or transition period that my last for 15-20 years, during which ovulation function and hormonal products decline. The climacteric can be divided into 3 stages: pre-, peri- and postmenopause. (Menopause is the point in time signaling the end of premenopause and the beginning of postmenopause.) xe2x80x9cPremenopausexe2x80x9d refers to the years when the menstrual cycle is regular, or most of the female reproductive life. It also refers to the early years of the climacteric, after the age of 40, when menstrual periods may become irregular and heavy. xe2x80x9cPerimenopausexe2x80x9d is the stage lasting several years on either side of the last menstrual period. This time marks many physical changes. xe2x80x9cMenopausexe2x80x9d means the final menstrual period when the female has not had a menstrual period for 12 months. xe2x80x9cPostmenopausexe2x80x9d overlaps with the end of the perimenopausal stage and extends into the years following the last menstrual period until the end of life.
During the reproductive years, two sources of estrogen production exist. The major source is the secretion of estradiol by granulosa cells of ovarian follicles. The second source involves extraglandular aromatization of plasma androstenedione. The endocrine change associated with the female climacteric are due mainly to the loss of estradiol. Cessation of estradiol secretion is attributed to loss of follicular granulosa cells and to a decreased responsiveness of these cells to follicle-stimulating hormones (FSH). These alterations cause the menstrual cycle initially to shorten and then gradually to lengthen as anovulaton occurs, and eventually to cease completely.
In postmenopausal women, estrogen production occurs almost exclusively by a mechanism known as xe2x80x9cperipheral or extraglandular aromatization.xe2x80x9d This utilizes circulating androstenedione, secreted primarily by the adrenals, and converts it to estrogen in tissue of fat, bone, muscle and brain. Little, if any, estrogen is derived from ovarian or adrenal secretion in menopausal women. In fact, plasma levels of estrogen do not change if the ovaries are removed after menopause. The estrogen production in post-menopausal women is characterized by the extraglandular formation of a biologically weaker estrogen, namely, estrone, rather than by the ovarian secretion of the potent estrogen, namely estradiol.
Although the quantity of testosterone secreted by the menopausal ovary does not change from previous levels, testosterone becomes the principal steroidal hormone secreted by the ovary. The growth of hair on the upper lip and chin of many elderly women may be due to diminished estrogen levels and unopposed action of testosterone in these women. Pubic auxiliary and scalp hair are partially lost, residual hair becomes coarser, mainly due to degeneration of skin and loss of skin appendages rather than to hormonal alterations.
Common symptoms associated with menopause are briefly described hereunder.
There exists a wide range of symptoms that commonly affect women during menopause. Despite the documented occurrence of all of the ailments, most medical texts recognize three major physical ailments, which are menstrual irregularity, hot flashes, and dry vagina (a.k.a. xe2x80x9cgenito-urinary distressxe2x80x9d). Osteoporosis is occasionally listed as a symptom, but it is really a condition beginning long before menopause, but which may become critical during the menopausal years. Psychological ailments (anxiety, depression and panic attacks) are viewed and handled differently depending on the source of the expert consulted.
Symptoms of menopause may be both long and short term. Short term symptoms include hot flashes, night sweats, loss of libido. Long term symptoms include the thinning and drying out of the vaginal and genital skin and urinary troubles, which may all become permanent. Standard sings of menopause are:
1) Menstrual irregularity, or a fluctuation in the menstrual cycle. Periods may continue to arrive in a timely manner, but there are usually minor changes. For example, the period that lasted 3 or 4 days may last for 2 or 6; the flow might be much grater than typical or the color of the flow may change. All of this is normal, as is the increasing tendency to skip a period.
2) Hot flashes and night sweats, are another very common physical symptom. A hot flash is the sudden sensation of heat. When experienced at night they are called night sweats. Cold chills are not uncommon either. A hot flash is described as a sudden onset of warmth in the face and neck that progresses to the chest, making the neck and face red. It is estimated that 75 to 85% of American women experience hot flashes, marked by a rise in body temperature and a feeling of unbearable heat. The veins of the hands may tingle and swell. Perspiration may bead at the hairline, between the breasts and down the back. Hot flashes can last from one minute to an hour, but they usually last 2 to 3 minutes and are frequently associated with dizziness, nausea, headaches and palpitations. They tend to appear during the time when menstrual periods are erratic and to peak during the year of the last menstrual period. They seem to occur most often just before rising and just before bed.
The combination of a rise in skin temperature, peripheral vasodilation, a transient increase in heart rate and changes in skin impedance is also known as vasomotor instability. 80% of women who experience hot flashes have symptoms for more than 1 year, but less than 25% have symptoms for more than 5 years. It is said than not all post menopausal women experience vasomotor symptoms, perhaps because of alterations in metabolism of catecholamine or catecholestrogen within the brain or because of extraglandular formation of estrone was sufficient in these women to suppress the symptoms. Thus, it appears that hot flashes are triggered by xe2x80x9cestrogen withdrawalxe2x80x9d rather than by a lack of estrogen. The exact mechanism(s) responsible for the vasomotor flush is unknown, although the hypothalamus is the likely site or origin of vasomotor flush.
3) Dry vagina and urinary distress. With menopause""s onset , the tissue of the urethra and vagina tend to thin out and become more fragile. The vagina may also become shorter and both urethra and vagina become more vulnerable to inflammation and infection. This atrophy of the epithelium ultimately leads to symptoms of irritation, burning, pruritis and vaginal bleeding at times. The loss of the vaginal epithelium correlates with the extent of estrogen deprivation and tends to worsen with time. This condition is likely to occur a few years after menopause and may mean that a women""s own lubrication is inadequate for pleasurable penile penetration. The reduction of lubrication during intercourse is due mainly to a decrease in vaginal fluids, blood flow and glycogen production.
More specifically, during reproductive years the vaginal pH is between 4.0 and 5.5 due to the production of glycogen-rich superficial cells. As ovarian function begins to wane, this maturational process is lost and the vaginal pH increases to a range between 6.0 and 8.0. These changes lead to a higher incidence of vaginitis.
Even when vaginal or urinary problems are relatively minor, many woman complain of frequent urination and a tendency to leak when coughing, sneezing or during orgasm. This is known as stress incontinence. Urge incontinence is diagnosed when urine is dribbled on the way to the toilet. Both conditions are treatable.
4) Osteoporosis, or xe2x80x9cporous bonexe2x80x9d, is a condition that results from excess loss of bone tissue. The onset is usually painless, with no advance warning, except for occasional lower back pain as crush fractures happen. Because the pain eases after a few days, few women suspect that a vertebra may have collapsed. The first awareness of osteoporosis for most women is a fracture of some sort.
Normally the amount of new bone formed is equal to or greater than that resorbed. In osteoporosis, bone resorption is greater than bone formation. Maximum bone density is reached between the ages of 25 and 36 years. By the age of 45 to 50, the rate of bone resorption is greater in women than in men and more prevalent in Caucasians than in blacks. After our mid-30""s, we begin to lose bone slowly at first and then more quickly in our late 40""s and early 50""s. Once menopause is past, bone loss slows down again.
Although we recognize an association between estrogen deprivation and progressive loss of bone mass, the role of estrogen in the pathogenesis of post menopausal osteoporosis is still not entirely clear. The balance between the rate of bone formation and resorption is complex and involves a sensitive relationship between dietary calcium intake and absorption , serum concentrations of calcium and phosphorus, and other issues. There are no specific estrogen receptors in bone, and estrogen per se does not stimulate osteoblastic activity. However, estrogen therapy does reduce urinary calcium excretion, (it is presumed) by increasing calcium absorption in the renal tubules.
Thus, while considerable evidence has accrued which lends credibility to the existence of a causal relationship between estrogen deprivation and osteoporosis, the issue of whether estrogen deprivation is the primary cause of osteoporosis has not been resolved. Generally, in estrogen deficient premenopausal women, bone loss is accelerated but corresponds more to the time of ovarian loss rather than to chronological age. Furthermore, women who are menstruating after age 50 have a slower rate of bone loss than do menopausal women of similar age.
5) Psychiatric Symptoms. The female climacteric may be quite stressful. Many menopausal women experience nervousness (easy excitability, mental and physical unrest), irritability (uncontrollable crying, frequent rage or anger), anxiety (feelings of apprehension, uncertainty, fear and loss of self-image), and depression (inability to make decisions, apathy, psychomotor retardation, loss of libido or loss of emotional reaction). Most scientists feel that depression is not hormone-dependent. And the diagnosis of xe2x80x9cinvolutional melancholiaxe2x80x9d which was previously used to describe menopausal depression, has been deleted from the list of acceptable diagnostic codes.
Additionally, the menopausal headache may have many causes which do not relate to estrogen deprivation, such as the hormonal therapy itself. Estrogen therapy alters REM (xe2x80x9crapid eye movementxe2x80x9d) sleep and the number of waking episodes associated with hot flashes in menopausal women.
We have come to learn the affect that our composition has on the climacteric only coincidentally after doing research related to the rheumotoid-based diseases. The compositions seems to extend the premenopause period, delaying menopause and therefore, postmenopause. The exact mechanism(s) responsible for this is unknown, although we suspect that certain component(s) of the composition stimulate the adrenal glands, counteracting the decline in estrogen production and encouraging the production of yet another hormone, cortisone.
With respect to the affect that the compositions have on rheumatoid-based diseases, we do not know how the inflammation triggering the onset of these diseases is controlled or abated, although this is the affect the compositions have.
Acute inflammatory dermatoses and chronic inflammatory dermatoses are usually mediated by local or systemic immunological factors, although their causes generally remain a mystery. Thousands of specific inflammatory dermatoses exist. Some have both acute and chronic stages, others are most characteristic in early or late stages. In general, acute lesions last form days to weeks and are characterized by inflammation, edema and sometimes, epidermal, vascular or subcutaneous injury. Chronic lesions, on the other hand, persist for months to years and often show significant components of altered epidermal growth (atrophy or hyperplasia) or dermal fibrosis.
Eczema falls into the category of acute inflammatory dermatoses. It is an umbrella clinical term embracing a number of pathogenetically different conditions. Al conditions are characterized by red, papoluvesicular, oozing and crusted lesions early on that with persistence eventuate into raised, scaling plaques. It has an acute phase which can become a chronic eruption if untreated. With time, persistent lesions become less xe2x80x9cwetxe2x80x9d (fail to ooze or form vesicles) and become progressively scaly.
Urticaria or hives refers to a common disorder of the skin characterized by localized mast cell degranulation and resultant dermal microvascular hypermeability falls into the category of acute inflammatory dermatoses. Individual lesions develop and fade usually within 24 hours, and episodes may last for days or persist for months. Persistent urticaria may simply be the result of inability to eliminate the causative antigen or may herald underlying diseases. Lesions may vary from small pruritic papules to large endematous plaques.
Erythema Multiforme falls into the category of acute inflammatory dermatoses. It appears to be a hypersensitivity response to certain infections and drugs. Patients have array of lesions including macules, papules, vesicles and bullae, as well as the characteristic target lesion consisting of a red macule or papule with a pale, vesicular or eroded center.
Psoriasis falls into the category of chronic inflammatory dermatoses. It is sometimes associated with arthritis, myopathy, enteropathy, spondylitic heart disease and AIDS. Psoriatic arthritis may be mild or produce deformities resembling the joint changes seen in rheumatoid arthritis. Most frequently affects elbows, knees, scalp, lumbosacral areas, and glans penis. Most typical lesion is well-demarcated, pink and salmon-colored plaque covered by loosely adherent scales that are characteristically silver-white in color. Psoriasis can be the cause of total body erythema and scaling known as erythroderma.
Lichen Planus falls into the category of chronic inflammatory dermatoses. Pruritic, purple, polygonal papules are signs of this skin disorder. It is self-limiting and generally resolves spontaneously one to two years after onset, often leaving zones of post-inflammatory hyperpigmentation. Oral lesions may persist for years. Lesions are itchy, flat-topped papules that may coalesce locally to form plaques often highlighted by white dots or lines called Wickman""s striae. Multiple lesions are characteristic and symmetrically distributed, particularly on the extremities, often about the wrists and elbows.
Gingivitis is the most common form of periodontal disease starting as inflammation of the marginal gingiva which is painless, although the gingiva may bleed on brushing. The disease spreads to involve the periodontal ligament and alveolar bone. As the alveolar bone is slowly resorbed, there is loss of periodontal ligament attachment between tooth and bone. The soft tissue separates from the tooth surface, causing xe2x80x9cpocketxe2x80x9d formation with bleeding on probing and during chewing. Acute inflammation may become superimposed on this chronic process, with the production of pus and formation of a periodontal abscess. Ultimately, extreme bone loss, tooth mobility, and recurrent abscess formation leads to tooth exfoliation or may mandate tooth extraction. It is infection associated with the accumulation of bacterial plaque which may become mineralized (xe2x80x9ccalculusxe2x80x9d) and which can be prevented by appropriate oral hygiene measures including tooth brushing, flossing, antibacterial mouth rinses, and the removal of impacted food debris.
Immunity Disorders. The prior art has proposed methods and compositions for improving the immune response of humans using dietary supplements from natural sources. Illustrative are U.S. Pat. Nos. 4,386,072; 5,602,109; and 5,731,290 which disclose vegetable oils such as oils of cotton seed, soybean, peanut, corn, sunflower seed, safflower, poppy seed, linseed and perilla for improving the immune response.
I. Topical Composition and Method of Treatment of Rheumatoid-Based Diseases
a) For the treatment of rheumatoid-based diseases the composition of the present invention comprises:
300 to 1500 grams, and preferably 700 to 1000 grams of finely divided powder of safflower seeds (carthamust inctorius 1) admixed into 6 to 7 gallons of warm water.
The method of treatment comprises:
bathing the patient in the composition for about 0.5 to 1.5 hours;
towel drying the patient;
allowing the residual composition to remain on the patient for 24 hours; and
repeating the treatment at least twice a week for 6 to 10 weeks or longer.
(b) In another embodiment the composition of the present invention comprises:
150 to 1000 grams, and preferably 300 to 800 grams of an extract of safflower seeds admixed into 6 to 7 gallons of warm water.
The method of treatment comprises:
bathing the patient in the composition for about 0.5 to about 1.5 hrs;
towel drying the patient;
allowing the residual composition to remain on the patient for 24 hours; and
repeating the treatment at least twice a week for 6 to 10 weeks or longer.
(c) Alternatively, the treatment of patients having rheumatoid-based diseases comprises massaging an extract of safflower seeds onto the affected joint areas of the patient for about 5 to 20 minutes, preferably for 10 to 15 minutes.
II. Compositions and Method of Treatment for Menopause
For the treatment of menopause a combination of topical and oral formulations are used. The topical treatment is as above-described in I(a) and I(b), except that the duration of treatment is extended for as long as necessary.
The oral component of the treatment comprises:
ingesting an oral formulation containing of from about 25 to 30 grams of an extract of safflower, or 30 to 100 grams of finely divided safflower seed twice a week as long as necessary.
While the compositions and treatments described in I and II above defines the specifics as best determined at present and supported by testing on human patients, it is to be understood that a broader aspect of the invention encompasses treatment of rheumatoid-based diseases and menopause by using a xe2x80x9ctherapeutically effective amountxe2x80x9d of said compositions. xe2x80x9cTherapeutically effective amountxe2x80x9d refers to the amount of an active agent sufficient to induce a desired biological result. That result is the alleviation of the signs, symptoms, or causes of the diseases or conditions described under Reported Developments.
III. Method of Treatment of: Inflammatory Diseases, such as Eczema, Urticaria, Psoriasis, Erythema Multiforme and Lichen Planus, Inflammation of the Gums, and Chronic Localized Bodily Pain Derived from Acute Injury
The treatment for the relief of inflammation and or pain associated with inflammatory dermatoses such as eczema, urticaria, psoriasis, erythema multiforme and lichen planus, gingivitis, and acute injury in a mammal comprises: topically administering to said mammal in need of such treatment a therapeutically effective amount of a finely divided powder of safflower seed having a particle size of 100 microns or less or its extract sufficient to induce alleviation of signs, symptoms or causes of inflammation or pain in a pharmaceutically acceptable carrier. The xe2x80x9cTherapeutically effective amountxe2x80x9d refers to the amount of an active agent sufficient to induce a desired biological result. That result is the alleviation of the signs, symptoms, or causes of the diseases or conditions described under Reported Developments. xe2x80x9cFinely divided powderxe2x80x9d denotes an average particle size of 100 microns or less.
IV. Method of Improving Immune Response
The method of treatment is preferably prophylactic, however, the treatment can also be advantageously used where the immune system is weakened by disease such as prostate, lung, stomach, esophagus and blood cancers. The method of prophylaxis and/or treatment comprising orally administering a prophylactically or therapeutically effective amount of safflower seeds or extract thereof sufficient to induce a desired biological result. The treatment comprises: ingesting an oral formulation containing of from about 25 to 30 grams of an extract of safflower seeds, or of from about 30 grams to about 100 grams of finely divided safflower seeds at least two to three times a week.
The active ingredient is preferably combined with food products such as jelly, cheese, ice cream, chocolate and beverages.
Alternatively, the safflower seeds or extract thereof may be incorporated into typical pharmaceutical carriers for convenience.
Oral pharmaceutical dosage forms are either solid or liquid. The solid dosage forms are tablets, capsules, granules, and bulk powders. Types of oral tablets include compressed, chewable lozenges and tablets, sugar-coated or film-coated. Capsules may be hard or soft gelatin capsules, while granules and powders may be provided in non-effervescent or effervescent form with the combination of other ingredients known to those skilled in the art.
Pharmaceutically acceptable carriers utilized in tablets are binders, lubricants, diluents, disintegrating agents, coloring agents, flavoring agents, and wetting agents. Sugar-coated tablets are compressed tablets to which different layers of pharmaceutically acceptable substances have been applied. Film-coated tablets are compressed tablets which have been coated with a water soluble polymers. Multiple compressed tablets are compressed tablets made by more than one compression cycle utilizing the pharmaceutically acceptable substances previously mentioned. Coloring agents may also be used in the above dosage forms. Flavoring and sweetening agents are used in compressed tablets, sugar-coated, multiple compressed and chewable tablets. Flavoring and sweetening agents are especially useful in the formation of chewable tablets and lozenges.
Examples of binders include glucose solution, acacia mucilage, gelatin solution, sucrose and starch paste. Lubricants include talc, starch, magnesium or calcium stearate, lycopodium and stearic acid. Diluents include, for example, lactose, sucrose, starch, kaolin, salt, mannitol and dicalcium phosphate. Disintegrating agents include corn starch, potato starch, bentonite, methylcellulose, agar and carboxymethylcellulose. Coloring agents include, for example, any of the approved certified water soluble FD and C dyes, mixtures thereof, and water insoluble FD and C dyes suspended on alumia hydrate. Sweetening agents include sucrose, lactose, mannitol and artificial sweetening agents such as sodium cyclamate and saccharin, and any number of spray dried flavors. Flavoring agents include natural flavors extracted from plants such as fruits and synthetic blends of compounds which produce a pleasant sensation. Wetting agents include propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate and polyoxyethylene laural ether. Film coatings include hydroxyethylcellulose, sodium carboxymethyl-cellulose, polyethylene glycol 4000 and cellulose acetate phthalate.
Liquid oral dosage forms include aqueous solutions, emulsions, suspensions, solutions and/or suspensions reconstituted from non-effervescent granules and effervescent preparations reconstituted from effervescent granules. Aqueous solutions include, for example, elixirs and syrups. Emulsions are either oil-in water or water-in-oil.
Elixirs are clear, sweetened, hydroalcoholic preparations. Pharmaceutically acceptable carriers used in elixirs include solvents. Syrups are concentrated aqueous solutions of a sugar, for example, sucrose, and may contain a preservative. An emulsion is a two-phase system in which one liquid is dispersed in the form of small globules throughout another liquid. Pharmaceutically acceptable carriers used in emulsions are non-aqueous liquids, emulsifying agents and preservatives. Suspensions use pharmaceutically acceptable suspending agents and preservatives. Pharmaceutically acceptable substances used in non-effervescent granules, to be reconstituted into a liquid oral dosage form, include diluents, sweeteners and wetting agents. Pharmaceutically acceptable substance used in effervescent granules, to be reconstituted into a liquid oral dosage form, include organic acids and a source of carbon dioxide. Coloring and flavoring agents are used in all of the above dosage forms.
Examples of preservatives include glycerin, methyl and propylparaben, benzoic acid, sodium benzoate and alcohol. Examples of non-aqueous liquids utilized in emulsions include mineral oil and cottonseed oil. Examples of emulsifying agents include gelatin, acacia, tragacanth, bentonite, and surfactants such as polyoxyethylene sorbitan monooleate. Suspending agents include sodium carboxymethylcellulose, pectin, tragacanth, Veegum and acacia. Diluents include lactose and sucrose. Sweetening agents include sucrose, syrups, glycerin and artificial sweetening agents such as sodium cyclamate and saccharin. Wetting agents include propylene glycol monostearate, sorbitan monooleate, diethylene glycol monolaurate and polyoxyethylene lauryl ether. Organic acids include citric and tartaric acid. Sources of carbon dioxide include sodium bicarbonate and sodium carbonate. Coloring agents include any of the approved certified water soluble FD and C dyes, and mixtures thereof. Flavoring agents include natural flavors extracted from plants such fruits, and synthetic blends of compounds which produce a pleasant taste sensation.
V. Method of Preventing or Minimizing Wrinkles in Facial Skin and Neck Areas of a Patient
a) For the prevention or minimization of facial and neck wrinkles the present invention comprises:
about 5 to 100 grams of finely divided powder of safflower seeds having an average particle size of about 100 microns or less or extract thereof for one application to the face and neck area of the patient.
The finely divided powder or its extract is applied to the site by rubbing the same by hand or by the use of a woven or non-woven cloth material, or cotton balls.
b) In another embodiment the present invention comprises:
about 0.4 to 25 grams of finely divided powder of safflower seeds having an average particle size of about 100 microns or less or extract thereof admixed in about 10 to 100 ml of purified water.
The mixture is applied by rubbing the mixture to the site by hand or by the use of a woven or non-woven cloth material or cotton balls.
c) In still another embodiment the present invention comprises:
about 0.4 to 25 grams of finely divided powder of safflower seeds, having an average particle size of 100 microns or less, or extract thereof combined with about 10 to 100 ml of a pharmaceutically acceptable carrier selected from the group consisting of lotions, creams or gels to form a composition. The composition is massaged into the face and neck of a patient.
d) Additionally, the finely divided powder or its extract can be made into a hot compress by impregnating a woven or non-woven fibrous wrap with said finely divided powder or its extract, dried and packaged for later use. Prior to the treatment the impregnated fibrous wrap is immersed in warm water and then applied to the face and neck of a patient.
Application of the various embodiments is at least once a day, more preferably two or three times a day. Subsequent to an application the face and neck are washed with warm tap water.